Nonvertebral Fragility Fractures Research Articles

Therapeutic Intervention for Osteoporosis of Surgical Cases With Non-Vertebral Fractures for Three Years in a Newly Established Rural Hospital in Japan.

Objectives Our hospital was newly opened in the spring of 2020 in a rural area of Japan, with a remarkably developing aging society and population decline. This study aimed to clarify and evaluate the practice of osteoporosis care in our hospital for three years since its establishment. We report a retrospective review of therapeutic interventions for osteoporosis for patients who underwent surgical treatment for non-vertebral fragility fractures in our hospital. Methods We evaluated the practice of osteoporosis intervention in patients who underwent surgery for proximal humerus fractures (PHFs), distal radius fractures (DRFs), or proximal femoral fractures (PFFs) from April 2020 to the end of March 2023. Results There were 115 surgical cases with non-vertebral fractures (10 patients with PHF, 41 patients with DRF, and 64 with PFF). Among the patients who had received osteoporosis treatment at other hospitals before the injury, only 15 (13.0%) patients had been administered therapeutic intervention for osteoporosis by other clinics or hospitals. Also, 82 (71.3%) patients were newly diagnosed with osteoporosis in our hospital after surgery according to the Japanese osteoporosis guideline. New postoperative osteoporosis interventions were administered to 39 (47.0%) patients, of which the rate was higher than the previous reports in Japan. While there was no significant difference between upper limb fracture and PFF in the percentage per young adult mean of spine areal bone marrow density (aBMD), the femoral neck aBMDs in the upper limb fracture group were significantly higher than in the PFF group. The serum total P1NP levels were significantly lower and the 25(OH)D levels were also greater in the upper limb fracture group than in the PFF group, whereas the serum TRACP-5b levels were not significantly different between the two groups. Two (1.7%) patients were affected with secondary fractures during the study period. Conclusions The rates of therapeutic intervention for osteoporosis of patients with non-vertebral fractures, especially in those with upper limb fractures, in our hospital were considered to be greater than those in the previous reports. However, the intervention rate for patients with PFFs was not much, and there was still room for improvement in our hospital concerning osteoporosis diagnosis and treatment.

Treatment options for postmenopausal osteoporosis

Osteoporosis is a systemic skeletal disease, characterized by a decrease of bone mass and bone quality, with a subsequent reduction of bone strenght and an increased risk of fracture. Hormone Therapy for menopausal women can significantly prevent osteopenia and osteoporosis, thus reducing the fracture risk. The use of HT, according to guidelines, is for postmenopausal women within 10 years since last menstruation or under the age of 60 years. Only HT at standard dose is able to reduce the fracture risk, while low-dose HT can prevent bone loss. Estrogens (with and without the addition of a progestin) and tibolone showed a fracture risk reduction effect. Also Tissue Selective Estrogen Complex (TSEC) can reduce the bone loss in postmenopause. For women without climacteric symptoms (as hot flushes and/or night sweats) the use of Selective Estrogen Receptor Modulators (SERMs) can be indicated, with a reduction of risk of vertebral fracture (for raloxifene and bazedoxifene), and non-vertebral fracture in high-risk women (for bazedoxifene). In more advence ages, antiresoptive agents as Bisphosphonates (Alendronate, Risedronate, Ibandronate and Zoledronate) can reduce the risk of vertebral, non-vertebral and hip fracture risk. Denosumab (DMAB), monoclonal antibobody against Rank-ligand (RANKL), providing an increased bone mass, significantly decreases risk of vertebral, non-vertebral and hip fracture. A drug holiday or treatment interruption is not recommended with DMAB, and DMAB dosing should not stopped without subsequent antiresorptive or other therapy to prevent a "rebound effect" with a possible increased risk of multiple vertebral fracture. Teriparatide (fraction 1-34 of recombinant PTH, administered daily 20 mcg sc) can stimulate osteoblast activity, with an important increase of bone mass and a significant reduction of risk of vertebral fracture, and of multiple vertebral fractures, but also of non-vertebral fragility fracture. Romosozumab (RMZ, adimnistered monlty 210 mg sc), is a bone-forming monoclonal antibody that binds to and inhibits sclerostin, with a dual effect of increasing bone formation and decreasing bone resorption. RMZ has showed to give marked increases in spine and hip bone density after 1 year of administration, also reducing fracture risk. The differences among the various treatments is the basis for the individualization of osteoporosis treatment, according to combination and/or sequential regimens of administration.

Treatment of osteoporotic fractures in alkaptonuria by teriparatide stimulates bone formation and decreases fracture rate – A report of two cases

Two cases of advanced alkaptonuria (AKU) with co-existing osteoporosis are described. Case 1 developed multiple non-vertebral fragility fractures, while Case 2 developed vertebral fragility fractures, both refractory to bisphosphonates. Difficulties in diagnosing osteoporosis in AKU complicated by extensive calcifying and ossifying spondylosis are discussed. Both patients continued to fracture despite nitisinone therapy for metabolic control of AKU, as well as bisphosphonate antiresorptive therapy for osteoporosis. Subsequently the patients were treated with teriparatide 20 μg subcutaneous injections daily for two years, leading to reduction in fractures soon after commencing therapy in both cases. Markers of bone remodelling P1NP and CTX were stimulated. No complications due hypercalcaemia or calcification were encountered in either case. We conclude that teriparatide is an effective adjunct in the treatment of AKU when bisphosphonates prove ineffective.

The Effect of Teriparatide Treatment on the Risk of Fragility Fractures in Postmenopausal Women with Osteoporosis: Results from the Asian and Latin America Fracture Observational Study (ALAFOS)

The Asian and Latin America Fracture Observational Study (ALAFOS) is a prospective, observational, single-arm study conducted in 20 countries across Asia, Latin America and the Middle East. ALAFOS evaluated new clinical vertebral and non-vertebral fragility fractures in relation to time on teriparatide, in postmenopausal women with osteoporosis in real-life clinical practice. Clinical fragility fractures, back pain, and health-related quality of life (HRQoL) were recorded in 6-month intervals for ≤ 24 months during teriparatide treatment and up to 12-months post-treatment. Data were analysed with piecewise exponential regression with inverse probability weighting for time to event outcomes and mixed-model repeated measures for back pain and HRQoL. 3054 postmenopausal women started teriparatide and attended ≥ one follow-up visit (mean [SD] age 72.5 [10.4] years). The median (95% CI) time to treatment discontinuation was 22.0 months (21.2, 22.8). During the treatment period, 111 patients (3.6%) sustained 126 clinical fractures (2.98 fractures/100 patient-years). Rates of new clinical fragility fractures were significantly decreased during the > 6–12, > 12–18, and > 18–24-month periods, as compared with the first 6 months of treatment (hazard ratio [HR] 0.57; 95% CI 0.37, 0.88; p = 0.012; HR 0.35; 95% CI 0.19, 0.62; p < 0.001; HR 0.43; 95% CI 0.23, 0.83; p = 0.011; respectively). Patients also reported an improvement in back pain and HRQoL (p < 0.001). These results provide data on the real-world effectiveness of teriparatide in the ALAFOS regions and are consistent with other studies showing reduction of fractures after 6 months of teriparatide treatment. These results should be interpreted in the context of the noncontrolled design of this observational study.

Dysmobility syndrome: a case-series study describing a musculoskeletal syndrome in postmenopausal Mexican women.

"Dysmobility Syndrome" (DS) correlates sarcopenia and osteoporosis together with mobility disturbances, obesity, fractures, and falls, all of which are related to adverse outcomes in the health of the elderly; however, there are no studies of DS in Mexican patients. In this study, we aimed to describe the characteristics of DS in Mexican postmenopausal women from a private practice. A case-series study was conducted; women of 60 years and older were invited to participate from August to December of 2019, a total of 50 patients were included. Medical history, physical tests, bone densitometry, and body composition analysis were performed; patients who met 3 or more of the following criteria were diagnosed with DS: osteoporosis: T-score ≤ -2.5, falls in a previous year, lean appendicular mass: ≤ 5.45 kg/m2, walking speed: < 1.0 m/s, grip strength: < 20 kg, and body fat percentage: > 40%. Out of the total 50 patients, 37 were diagnosed with DS, with a prevalence of 74% in our study. Sixteen patients had a history of a non-vertebral fragility fracture, of which 14 had a diagnosis of DS (87%). DS has a high frequency in our study group, and was found to be closely related to the presence of non-vertebral fragility fractures. More research is needed to describe the prevalence and characteristics of DS with a stronger statistical significance within our population, and among others across the country, to get an extensive understanding of its presentation in Mexican women. • The frequency of DS in this study is higher than the one that is described in global literature. • DS diagnosis is closely related to the antecedent of non-vertebral fragility fracture.

Retrospective analysis of the use of osteoporosis medication at the presentation of non-vertebral fragility fractures in a predominantly Hispanic population.

Background: Despite the high incidence of osteoporosis, many patients at risk of fragility fractures may not initiate treatment due to concerns about side effects, cost or under-diagnosis, such as the case of vertebral fractures. We aimed to identify whether the patient population with non-vertebral fragility fractures where already receiving prophylactic treatment for osteoporosis at presentation within a regional hospital in the southernmost region of the United States. This region is characterized by a high number of patients from Hispanic/Latino heritage (80%) and reduced access to healthcare services. Methods: We conducted a three-year, retrospective cohort study of patients presenting with low impact fractures of the humerus or the shoulder griddle, lower end of radius or ulna and forearm, hip fractures (femoral neck, intertrochanteric/ subtrochanteric), and ankle fractures. Male and female subjects of 50 years or older were included. Demographic data and information on medications reported at fracture presentation were extracted from electronic medical records. Results: We found that 42% of the patients were taking at least one medication to prevent osteoporosis. The predominant combination was vitamin D plus calcium and bisphosphonates. If patients taking only vitamin D plus calcium are excluded, 16.7% of the sample took osteoporosis medications at the fragility fracture presentation. The likelihood of taking osteoporosis medication was increased by age and type of health insurance (Medicare/private insurance), and concomitant diagnosis of impaired gait and mobility. The percentage of the patients taking prophylactic medications for osteoporosis at the time of a fragility fracture was comparable to reported national standards and associated with increased age and health insurance coverage. Conclusion: In a predominantly Hispanic/Latino patient population living in a medically underserved region, there is substantial recognition and prevention strategies for osteoporosis.

Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis

ObjectivesEmerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the efficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture. MethodThe Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with −1.0 > bone mineral density (BMD) T-score > −2.5 (low bone mass) and those with BMD T-score ≤ −2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up. ResultsFull-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36–0.71) and significantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70%–5.14%). At the hip, this value was 2.94% (95%CIs = 2.13%–3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene significantly decreases the risk of subsequent clinical vertebral fractures. ConclusionThe bisphosphonates are efficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis.

How to improve the outcomes of surgically treated proximal humeral osteoporotic fractures? A narrative review.

Proximal humeral fractures (PHF) are the third most common non-vertebral fragility fractures after hip and distal radius. It still controversial which treatment might be more appropriate, and surgically treated outcomes depends also on an appropriate technique. In order to clarify surgical indications, tips and pitfall a narrative review was conducted. Pinning, external fixation, plating and internal fixators has each one its advantages and disadvantages. During the procedure an appropriate use of the fixation device and handling of the soft tissue might be associated with better outcomes. Calcar comminution, varus angulation, medial dislocation of the shaft, fracture-dislocation are factors that could lead to choose a replacement. Hemiarthroplasty and reverse total shoulder arthroplasty are the most common prosthesis used in PHF. The restoration of humeral length and tuberosities might lead to an improvement in clinical outcomes and prosthesis survivorship.

Osteoporosis-related Vertebral Fragility Fractures: A Review and Analysis of the American Orthopaedic Association's Own the Bone Database.

Retrospective cohort study of the Own the Bone database which is a fracture liaison service designed to improve recognition and treatment of osteoporosis. To use the Own the Bone (OTB) database to 1) examine the specific demographics of patients presenting with a low-energy clinical vertebral fracture (VFX) and 2) compare demographic and fracture-specific risk factors between patients with clinical VFX versus patients with nonvertebral low-energy fracture (NVFX). Large database studies have described risk factors for developing VFX. It is well described that a history of previous VFX portends an increased risk of future VFX. Few studies have reported cohorts from a fracture liaison service such as the OTB initiative. 35,039 unique cases of fragility fracture occurred between 2009 and 2016 and were included in analysis. VFX accounted for 3395 (9.9%) of the presenting fractures at OTB enrollment. The demographics, lifestyle factors, medication use, and fracture-specific data for patients in the OTB registry with vertebral fractures were summarized and then statistically compared to those with nonvertebral fragility fractures. The majority of VFX patients were Caucasian, postmenopausal women (74.4%). There was an increased likelihood of presenting with a vertebral fracture in patients who sustained a previous VFX after the age of 50, while patients who sustained a prior nonvertebral fracture (NVFX) were more likely to present with a subsequent NVFX. After controlling for patients with a history of fracture after the age of 50, VFX patients (vs. NVFX) were more likely to be age 70-79, class 1 obesity, with a history of taking anti-osteoporotic prescription medications. Multiple factors were associated with a significantly increased risk of VFX compared with NVFX. Understanding the risk factors unique to fragility VFX is a critical component for targeting "at-risk" patients and preventing future osteoporosis-related fractures and their consequences. 4.

Psychotropic medications and proton pump inhibitors and the risk of fractures in the teriparatide versus risedronate VERO clinical trial.

VERO is a fracture endpoint study in women with established osteoporosis that showed reduction in the risks of new vertebral fractures (VFx) and clinical fractures in women randomized to teriparatide compared with risedronate. Patients on psychotropic drugs (hypnotics, benzodiazepines and antidepressants [selective serotonin- and norepinephrine-reuptake inhibitors: SSRIs and SNRIs]) and proton pump inhibitors (PPIs) may be at a higher risk of fractures. We studied the association of exposure to these medications with the risk of fractures in the VERO study cohort, including an assessment of their potential interactions with the assigned clinical trial drugs. A total of 1360 postmenopausal women with at least 2 moderate or 1 severe VFx and bone mineral density T-score ≤-1.50 were randomized to subcutaneous daily teriparatide (20μg) or oral weekly risedronate (35mg) in a double-blind, double-dummy, 2-year trial. In thispost-hoc analysis, multivariable log-binomial and Cox proportional hazards regression models were used to estimate adjusted risk ratios (RR) or hazard ratios (HR) for the exposure to these concomitant medications with the occurrence of incident fractures. We also assessed treatment effect modifications on anti-fracture efficacy driven by the use of these medications. There were 406 (29.9 %), 347 (25.5 %) and 176 (12.9 %) subjects taking PPIs, benzodiazepines/hypnotics, and SSRIs/SNRIs during the study, respectively. For all fracture endpoints, the greater risk reduction of teriparatide versus risedronate did not significantly differ within the categories of psychotropic drugs and PPIs. Multivariable analysis showed that the risk of pooled new and worsened VFx was higher in PPI users than in non-PPI users (RR: 1.57; p=0.032), regardless of the study treatment. Benzodiazepine/hypnotic drug users showed an increased risk of clinical fractures (HR: 1.71; p=0.026) and non-vertebral fragility fractures (NVFFx, HR: 1.89; p=0.017), regardless of the study treatment. Increases in the risk of clinical fractures (HR: 1.93; p=0.018) and NVFFx (HR: 2.16; p=0.011) were also observed in SSRI/SNRI users, regardless of the study treatment. In postmenopausal women with severe osteoporosis, the superior anti-fracture efficacy of teriparatide compared with risedronate was consistent regardless of psychotropic or PPI drugs use. Patients taking psychotropic drugs and PPIs showed a higher risk for NVFFx and VFx respectively, compared to those not on these medications.

Fracture Prevention with Zoledronate in Older Women with Osteopenia

BackgroundBisphosphonates prevent fractures in patients with osteoporosis, but their efficacy in women with osteopenia is unknown. Most fractures in postmenopausal women occur in those with osteopenia, so therapies that are effective in women with osteopenia are needed.MethodsWe conducted a 6-year, double-blind trial involving 2000 women with osteopenia (defined by a T score of −1.0 to −2.5 at either the total hip or the femoral neck on either side) who were 65 years of age or older. Participants were randomly assigned to receive four infusions of either zoledronate at a dose of 5 mg (zoledronate group) or normal saline (placebo group) at 18-month intervals. A dietary calcium intake of 1 g per day was advised, but calcium supplements were not provided. Participants who were not already taking vitamin D supplements received cholecalciferol before the trial began (a single dose of 2.5 mg) and during the trial (1.25 mg per month). The primary end point was the time to first occurrence of a nonvertebral or vertebral fragility fracture.ResultsAt baseline, the mean (±SD) age was 71±5 years, the T score at the femoral neck was −1.6±0.5, and the median 10-year risk of hip fracture was 2.3%. A fragility fracture occurred in 190 women in the placebo group and in 122 women in the zoledronate group (hazard ratio with zoledronate, 0.63; 95% confidence interval, 0.50 to 0.79; P<0.001). The number of women that would need to be treated to prevent the occurrence of a fracture in 1 woman was 15. As compared with the placebo group, women who received zoledronate had a lower risk of nonvertebral fragility fractures (hazard ratio, 0.66; P=0.001), symptomatic fractures (hazard ratio, 0.73; P=0.003), vertebral fractures (odds ratio, 0.45; P=0.002), and height loss (P<0.001).ConclusionsThe risk of nonvertebral or vertebral fragility fractures was significantly lower in women with osteopenia who received zoledronate than in women who received placebo. (Funded by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12609000593235.)

Sex hormone–binding globulin is a biomarker associated with nonvertebral fracture in men on dialysis therapy

Gonadal hormones impact bone health and higher values of sex hormone-binding globulin (SHBG) have been independently associated with fracture risk in men without chronic kidney disease. People with chronic kidney disease have a greatly increased fracture risk, and gonadal dysfunction is common in men receiving dialysis treatment. Nevertheless, in these men the effect of gonadal steroids and SHBG on bone mineral density (BMD) and fracture risk is unknown. Here we investigate relationships between gonadal steroids, SHBG, BMD and fracture in men on long-term dialysis therapy, awaiting kidney or simultaneous pancreas kidney transplantation. Results of serum biochemistry, SHBG, gonadal steroids (total testosterone, calculated free testosterone and estradiol), BMD by dual-energy X-ray absorptiometry and thoracolumbar X-rays were obtained. Multivariable regression models were used to examine associations between SHBG, gonadal steroids, BMD and fracture of 321 men with a mean age of 47 years. Diabetes mellitus was present in 45% and their median dialysis vintage was 24 months. Prior fractures occurred in 42%, 18% had vertebral fracture on lateral spine X-ray, 17% had non-vertebral fragility fracture within 10 years and 7% had both. After adjustment for age, body mass index and dialysis vintage, higher SHBG levels were significantly associated with nonvertebral fractures [odds ratio 1.81 (1.30-2.53)] and remained significant after adjustment for BMD. Calculated free testosterone and estradiol values were not associated with fracture. Prevalent fracture rates were high in relatively young men on dialysis awaiting transplantation. Thus, SHBG is a novel biomarker associated with fracture, which warrants investigation in prospective studies.

Shizofrenija i osteoporoza

Schizophrenia (SCH) is a complex mental disorder that affects about 1% of the population. SCH is characterized by positive symptoms, negative symptoms and cognitive impairment. SCH patients often require a long-term treatment with antipsychotics. Unfortunately, treatment with antipsychotics can often be followed with metabolic side effects, decrease of bone mineral density (BMD) and osteoporotic fractures. Osteoporosis is a degenerative disease characterized by decreased bone stiffness, as signified by low bone mineral density, vertebral or nonvertebral fragility fractures and disruption of bone microarchitecture. Decreased BMD and increased incidence of fractures are described in SCH patients treated for a long time with antipsychotics . On the other hand, deterioration of bones and metabolic disturbances are seen in SCH patients who have never received antipsychotics. It remains unclear if the observed changes of bones consequence of disease process itself or antipsychotics are responsible, together with characteristic life style of patients that usually include smoking, poor nutrition, sedentary and low vitamin D. The mechanisms of antipsychotic-induced osteoporosis are complex. The most possible one is hyperprolactinemia. Hyperprolactinemia might directly affect bone turnover by stimulating bone resorption relative to bone formation. Also, prolonged hyperprolactinemia may cause hypogonadotropic hypogonadism, resulting at the end in impaired suppression of sex hormones and ultimately in changes in bone metabolism. On the other hand, bone remodeling is also controlled by the hypothalamic-pituitary-adrenal (HPA) axis. Dysregulation of HPA axis activity is consistently described in SCH patients. Perinatal phencyclidine (PCP) administration to rodents represents an animal model of SCH. This model is suitable for the investigations if the changes of bones are a consequence of disease itself or applied antipsychotics. Furthermore, it can be used to clarify the mechanism of action of PCP and chronic treatment with antipsychotics on bone structure and body composition, in order to prevent the occurrence of osteoporosis.

Adding VFA to DXA Identifies Fracture Risk in a Way Not Duplicated by Other Measures

Published studies have demonstrated that adding vertebral fracture assessment (VFA) to dual-energy X-ray absorptiometry (DXA) identifies more patients with increased fracture risk than DXA alone. But who needs VFA? This study attempts to determine if some test other than VFA could duplicate the additional information obtained by performing VFA on all first-time patients. This study looked at the Fracture Risk Assessment Tool (FRAX), height loss, age, documented back pain, and nonvertebral fragility fractures. VFA was performed on 1,259 (all) DXA patients at their first visit from March 2010 through September 2013. All DXA and VFA results were read by the same International Society for Clinical Densitometry-certified clinician. By DXA alone, 44% were osteoporosis. Adding VFA increased clinical osteoporosis by 36% of the original total patients. Eighty-three "normal bone mineral density" patients were changed to clinical osteoporosis. FRAX identified 53% of the patients with diagnosis changes. Historical height loss was not reliable. Increasing age correlated only weakly with clinical osteoporosis. These are modest numbers from a nonacademic referral practice and may not be typical of other populations. Thirty-six percent of our patients were misclassified by DXA alone, with fragility fractures already taken into account for T-scores of -1.5 and lower. FRAX, height loss, age, back pain, and fragility fractures all failed to identify many of the patients identified by VFA. Seeing the lateral spine images obtained by VFA influenced patients and families. VFA on all first-time patients should be reconsidered. BMD = bone mineral density DXA = dual-energy X-ray absorptiometry FRAX = Fracture Risk Assessment Tool HL = height loss ISCD = International Society for Clinical Densitometry VF = vertebral fracture VFA = vertebral fracture assessment.

Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial

No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome. We compared the anti-fracture efficacy of teriparatide with risedronate in patients with severe osteoporosis. In this double-blind, double-dummy trial, we enrolled post-menopausal women with at least two moderate or one severe vertebral fracture and a bone mineral density T score of less than or equal to -1·50. Participants were randomly assigned to receive 20 μg of teriparatide once daily plus oral weekly placebo or 35 mg of oral risedronate once weekly plus daily injections of placebo for 24 months. The primary outcome was new radiographic vertebral fractures. Secondary, gated outcomes included new and worsened radiographic vertebral fractures, clinical fractures (a composite of non-vertebral and symptomatic vertebral), and non-vertebral fractures. This study is registered with ClinicalTrials.gov (NCT01709110) and EudraCT (2012-000123-41). We enrolled 680 patients in each group. At 24 months, new vertebral fractures occurred in 28 (5·4%) of 680 patients in the teriparatide group and 64 (12·0%) of 680 patients in the risedronate group (risk ratio 0·44, 95% CI 0·29-0·68; p<0·0001). Clinical fractures occurred in 30 (4·8%) of 680 patients in the teriparatide group compared with 61 (9·8%) of 680 in the risedronate group (hazard ratio 0·48, 95% CI 0·32-0·74; p=0·0009). Non-vertebral fragility fractures occurred in 25 (4·0%) patients in the teriparatide group and 38 (6·1%) in the risedronate group (hazard ratio 0·66; 95% CI 0·39-1·10; p=0·10). Among post-menopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures is significantly lower in patients receiving teriparatide than in those receiving risedronate. Lilly.

Vertebral fracture assessment in patients presenting with a non-hip non-vertebral fragility fracture: experience of a UK Fracture Liaison Service.

Most vertebral fragility fractures (VFF) have no history of trauma. Vertebral fracture assessment (VFA) during dual energy x-ray absorptiometry (DXA) can be used to detect these VFFs. This study aims to identify the prevalence of undiagnosed VFF in patients presenting with a non-hip non-vertebral fragility fracture. Patients identified by the fracture liaison service (FLS) of a large UK university hospital presenting with a non-hip non-vertebral fragility fracture were evaluated from 1 January 2012 to 30 September 2015. Local protocol identified those that would proceed for VFA. Data was collected on patient characteristics, fracture details, bone mineral density (BMD) measurements and VFA results. Five hundred sixty-seven patients (mean (SD) age, 72 (9.4) years) of mostly women (88.3%) had a VFA performed as part of their DXA assessment. One hundred forty-three patients (25.2%) were identified to have a vertebral fracture, of whom 57.3% of them had one fracture. 49.5% of those with vertebral fractures had BMD measurements diagnostic of osteoporosis. Mean (SD) age was higher in those with vertebral fractures compared to those without; 74.9 (8.3) years vs 70.4 (9.5) years, p<0.00. Those aged 75years and over were more likely to have multiple fractures than those younger than 75years (16.3 vs 4%, p=0.01). A quarter of patients presenting with a non-hip non-vertebral fragility fracture have an undiagnosed vertebral fracture. Older people are more likely to have vertebral fractures and more likely to have multiple fractures. VFA during bone densitometric assessment can further aid stratifying future fracture risk.

Safety and effectiveness of daily teriparatide for osteoporosis in patients with severe stages of chronic kidney disease: post hoc analysis of a postmarketing observational study.

Teriparatide (recombinant 1–34 N-terminal sequence of human parathyroid hormone) for the treatment of osteoporosis should be prescribed with caution in patients with severe stages of chronic kidney disease (CKD). However, in clinical settings, physicians and surgeons who treat such patients have few available options. We sought to further explore the safety and effectiveness of teriparatide for the treatment of osteoporosis in Japanese patients with severe stages of CKD. This was a post hoc analysis of a postmarketing surveillance study that included patients with osteoporosis at high risk of fracture and stage 4 or 5 CKD. Patients received subcutaneous teriparatide 20 μg daily for up to 24 months. Safety profiles were assessed by physician-reported adverse drug reactions (ADRs). Effectiveness was assessed by measuring bone formation (via procollagen type 1 N-terminal propeptide [P1NP]), bone mineral density (BMD), and the incidence of clinical vertebral or nonvertebral fragility fractures. A total of 33 patients with severe stages of CKD (stage 4, n=30; stage 5, n=3) were included. All patients were female, and 81.8% had a history of previous fracture. No serious ADRs were recorded; a total of 4 ADRs were recorded for 4 of 33 patients. Increases in BMD and P1NP levels were observed both overall and in most individual patients. New fractures occurred in 1 patient with stage 5 CKD, but not in patients with stage 4 CKD. In this post hoc analysis conducted in Japan, teriparatide appeared to be effective for the treatment of osteoporosis in elderly female patients with severe stages of CKD, and no new safety concerns were observed.

Older men with severe disc degeneration have more incident vertebral fractures-the prospective MINOS cohort study.

Data on the relationship between disc degeneration (DD) and fragility fractures in men are limited. The aim of this study was to prospectively analyse the risk of vertebral and non-vertebral fractures in men with thoracolumbar DD according to the severity of its radiological signs: disc space narrowing (DSN), osteophytes and endplate sclerosis. Men >50 years of age (n = 765) had lateral spine radiographs and DXA and were monitored prospectively. We analysed the risk of incident vertebral (7.5 years) and non-vertebral fractures (10 years) in men according to the severity of DD. After adjustment for age and weight, BMD increased with increasing total DSN score, endplate sclerosis and osteophytosis. Over 7.5 years, 28 incident vertebral fractures occurred in 27 men. After adjustment for age, BMI, spine BMD, prior fractures and abdominal aortic calcifications, the vertebral fracture risk was 3-fold higher in the upper DSN quartile vs men without DSN. After adjustment for the same confounders, vertebral fracture risk was also nearly 3-fold higher in the upper DSN quartile vs the three lower quartiles combined. Over 10 years, 61 men sustained non-vertebral fragility fractures. After adjustment for age, BMI, hip BMD, abdominal aortic calcifications and prior falls and fractures, the non-vertebral fracture risk decreased with increasing DSN score. The risk of non-vertebral fracture was half as high in men above the median total DSN score vs men below the median. In older men, severe DD is associated with higher BMD. Multilevel severe DSN is associated with higher vertebral fracture risk and lower non-vertebral fracture risk.

Patients with prior vertebral or hip fractures treated with teriparatide in the Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) observational study

In patients in the Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) observational study with and without a prior vertebral or hip fracture, the incidence of nonvertebral fractures was lower with >6 months of teriparatide treatment than during the first 6 months. Clinical evidence on the effect of teriparatide in patients with prior fracture is limited. In the DANCE observational study, the incidence of nonvertebral fragility fractures (NVFX) decreased significantly in patients receiving teriparatide for >6 months (6-24 months) versus >0 to ≤6 months (reference period). We performed a post hoc analysis to assess the effect of teriparatide 20 μg/day in patients who entered DANCE with prior vertebral or hip fractures. The incidence of patients experiencing a NVFX for four 6-month intervals during and after treatment was compared with the reference period. Overall, 4085 patients received ≥1 dose of teriparatide. Of 3720 with sufficient data for efficacy analysis, 692 had prior vertebral fracture, including 179 with previous kyphoplasty/vertebroplasty; 290 had prior hip fracture. These patients were older, and those with prior vertebral fractures had more comorbid conditions at baseline than those without prior vertebral fractures. The incidence of patients experiencing NVFX declined over time in all patient groups. The fracture incidence rate declined 49 and 46%, respectively, in patients with and without prior vertebral fracture and was 63 and 46% lower in patients with previous kyphoplasty/vertebroplasty and without prior vertebral fracture. NVFX declined 43 and 48% in patients with and without prior hip fracture. The reduced incidence over time was consistent in the subgroups (all interaction p values >0.05). Patients with prior fracture were more likely to experience serious adverse events. The incidence of NVFX decreased over time in patients receiving teriparatide in DANCE regardless of prior fracture status.

Measurement of cortical porosity of the proximal femur improves identification of women with nonvertebral fragility fractures

SummaryWe tested whether cortical porosity of the proximal femur measured using StrAx1.0 software provides additional information to areal bone mineral density (aBMD) or Fracture Risk Assessment Tool (FRAX) in differentiating women with and without fracture. Porosity was associated with fracture independent of aBMD and FRAX and identified additional women with fractures than by osteoporosis or FRAX thresholds.IntroductionNeither aBMD nor the FRAX captures cortical porosity, a major determinant of bone strength. We therefore tested whether combining porosity with aBMD or FRAX improves identification of women with fractures.MethodsWe quantified femoral neck (FN) aBMD using dual-energy X-ray absorptiometry, FRAX score, and femoral subtrochanteric cortical porosity using StrAx1.0 software in 211 postmenopausal women aged 54–94 years with nonvertebral fractures and 232 controls in Tromsø, Norway. Odds ratios (ORs) were calculated using logistic regression analysis.ResultsWomen with fractures had lower FN aBMD, higher FRAX score, and higher cortical porosity than controls (all p < 0.001). Each standard deviation higher porosity was associated with fracture independent of FN aBMD (OR 1.39; 95 % confidence interval 1.11–1.74) and FRAX score (OR 1.58; 1.27–1.97) in all women combined. Porosity was also associated with fracture independent of FRAX score in subgroups with normal FN aBMD (OR 1.88; 1.21–2.94), osteopenia (OR 1.40; 1.06–1.85), but not significantly in those with osteoporosis (OR 1.48; 0.68–3.23). Of the 211 fracture cases, only 18 women (9 %) were identified using FN aBMD T-score < −2.5, 45 women (21 %) using FRAX threshold >20 %, whereas porosity >80th percentile identified 61 women (29 %). Porosity identified 26 % additional women with fractures than identified by the osteoporosis threshold and 21 % additional women with fractures than by this FRAX threshold.ConclusionsCortical porosity is a risk factor for fracture independent of aBMD and FRAX and improves identification of women with fracture.